Predisposition to essential hypertension and the development of diabetic nephropathy

Only a subset of insulin-dependent diabetic patients are at risk of developing nephropathy. Prospective studies of uncomplicated insulin-dependent diabetic cohorts have shown that a rise in systemic arterial pressure is a concomitant feature of the progression to early nephropathy. The development of hypertension is an integral feature of established nephropathy in diabetes, and its amelioration retards the progression of disease and may improve overall mortality. Family studies have suggested that nondiabetic parents of insulin-dependent diabetic patients with nephropathy have a greater prevalence of hypertension, and in certain groups of non-insulin dependent patients, it has been found that the blood pressure before the onset of diabetes correlates with the development of nephropathy after the onset of diabetes. These results indicate that a propensity to hypertension may be part of the genetic predisposition to nephropathy. This contention is further supported by the finding that a raised erythrocyte sodium-lithium countertransport, a biochemical marker of hypertension and cardiovascular disease whose activity is largely genetically determined, occurs with greater frequency in proteinuric diabetic patients and their nondiabetic parents than in those diabetic patients without nephropathy and their parents. Recent family studies have also shown that a family history of cardiovascular disease significantly increases the risk of nephropathy by up to three-fold in insulin-dependent diabetes. It is suggested that the cardiorenal complications of diabetes mellitus may be linked to reduced insulin sensitivity, which itself is associated with hypertension, raised sodium-lithium countertransport rates, and cardiovascular disease.